Health Care Utilization Determined From Administrative Claims Analysis for Patients Who Received Inhaled Corticosteroids With Either Montelukast or Salmeterol

Drs. Crownover and Curtiss published separate editorials that made reference to our article on health care utilization among patients with asthma who were treated with inhaled corticosteroids (ICSs) in combination with either montelukast (MON) or salmeterol (SAL). The subject of Crownover's editorial is application of the PP-ICONS tool to skim research articles to quickly evaluate new publications. The Curtiss editorial more broadly discusses asthma disease management. Both the Crownover and Curtiss editorials reference the NAEPP guidelines for diagnosis and management of asthma. Curtiss states that leukotriene modifiers (LMs) are recommended for only one category of patient, those in Step 3 with moderate persistent asthma.(2, p. 344) In fact, LMs are listed in the guidelines as alternative treatment for both mild persistent and moderate persistent asthma for infants and young children (aged 5 years and younger) and for adults and children older than 5 years.


■■ Health Care Utilization Determined From Administrative Claims Analysis for Patients Who Received Inhaled Corticosteroids With Either Montelukast or Salmeterol
To the Editor: Drs. Crownover 1 and Curtiss 2 published separate editorials that made reference to our article 3 on health care utilization among patients with asthma who were treated with inhaled corticosteroids (ICSs) in combination with either montelukast (MON) or salmeterol (SAL). The subject of Crownover' s editorial is application of the PP-ICONS tool 4 to skim research articles to quickly evaluate new publications. The Curtiss editorial more broadly discusses asthma disease management. Both the Crownover and Curtiss editorials reference the NAEPP guidelines for diagnosis and management of asthma. Curtiss states that leukotriene modifiers (LMs) are recommended for only one category of patient, those in Step 3 with moderate persistent asthma. (2, p. 344) In fact, LMs are listed in the guidelines as alternative treatment for both mild persistent and moderate persistent asthma for infants and young children (aged 5 years and younger) and for adults and children older than 5 years. 5 Our study showed a higher rate of emergency department (ED) and hospital visits among the ICS/SAL group compared with the ICS/MON group. However, we also observed greater short-acting beta-agonist (SABA) use among the ICS/MON patients. Crownover is troubled by the contrast between these findings for ED/hospitalization versus SABA use. It should be noted that there is no agreed-upon method to measure total beta-agonist use (i.e., SABA + long-acting beta-agonist [LABA]) among patients taking both SABA and LABA. This conundrum makes it difficult to interpret asthma control by simply observing SABA use in patients using ICS/SAL. Thus, alternative interpretations of the data should be considered.
The data from our study could suggest that although many patients may be controlled on LABA, a small number of these patients (but more than expected) may need ED or hospital care for serious asthma episodes. This finding may be consistent with the findings from the Salmeterol Multicenter Asthma Research Trial (SMART) and the warnings for LABA. [6][7][8] It is curious that this result in our study was largely driven by the subset of ICS/SAL patients who did not have prior ICS use, but this finding appears to be supportive of using step care to initiate ICS/SAL combination asthma therapy, and not using ISC/SAL in combination as first-line treatment.
Curtiss suggested that our finding on SABA use may be more clinically significant than the ED and hospitalization finding. The observed SABA use translates into approximately 1.2 canisters per person per year (4.36 versus 3.16) more for the ICS/MON group. In contrast, the observed ED visits after starting the treatment regimens across the total population were 3 per 100 patients per year in the ICS/MON group versus 7 per 100 patients per year in the ICS/SAL group. These measures are likely to represent different aspects of asthma control. ED/ hospitalizations typically occur with more problematic acute severe exacerbations, while SABA prescriptions may be a marker for day-to-day symptoms (though interpreting SABA use alone is difficult in patients using LABA, as previously mentioned). Which of these measures is more clinically important depends on one' s perspective, although serious exacerbations represent significant morbidity (and potential mortality) for patients as well as costly resource utilization for the health care system.
It is difficult to know whether all factors that should potentially confound the results are accounted for in any retrospective database study. Curtiss asserted that we failed to use the 4-level disease severity proxy measure to obtain propensity scores for matching the treatment groups. This is incorrect (Refer to tables 1 and 2 of our paper). The use of a proxy severity measure in our research 3 was also described in Crownover' s editorial as a post hoc analysis that occurred during the review process for our study. Matching by propensity score, including the 4-level disease severity proxy, was conducted prior to our submission to the journal; it was not post hoc. During the review process, we were asked to include a table of our propensity model in the paper to provide more detail on this aspect of the methods; we complied with this request. After propensity matching, there was no statistically significant difference in the variables measured (Table 2 of our paper), including the proxy severity measure. Crownover suggested that perhaps only 25% of the cases (the more severe cases by the proxy measure) could have been included in our analyses. Deleting 75% of the cases that matched between the treatment groups would not be representative of how these products were being used in clinical practice during the time frame of our study. The total sample in our study (N = 1,216 subjects) represents 608 ICS/MON patients and 608 ICS/SAL patients that were matched using a propensity score model that accounted for a wide range of pretreatment characteristics. Based on the available data, there was no indication that the treatment groups differed in any dimensions that would skew the results in favor of montelukast.
The value of asthma therapy is multidimensional, and different patients may require different approaches to treatment due to the heterogeneity of response among patients diagnosed with asthma. The data from our study 3 provide further insights on important asthma outcomes associated with use of ICS/MON or ICS/SAL in clinical practice.